| 11 | 0 | 0 |
| Downloads | Citas | Reads |
Porcine bacterial pathogens pose a serious threat to the healthy development of the pig industry, and inactivated vaccines have become the primary prevention and control means.High-density fermentation technology is crucial for achieving large-scale, and efficient production of antigens.To address the issues such as low proliferation efficiency of bacteria and significant batch-to-batch antigen variability caused by insufficient nutrient adaptation, metabolic inhibition, and environmental instability during high-density fermentation, we review the optimization strategies for key factors including nutrient consumption patterns, culture conditions, and fermentation processes.Moreover, we systematically summarize the optimization strategies for various nutritional components such as carbon sources, nitrogen sources, inorganic salts, serum, and NAD cofactors, deeply analyze the mechanisms underlying critical culture conditions such as temperature, pH value, and dissolved oxygen, and summarize the characteristics and applications of fermentation processes under different feedback signals.Furthermore, we put forward key suggestions such as in-depth optimization of culture media, multi-faceted modification of strains, and multi-strain co-fermentation.The review provides solid theoretical supports and clear development directions for the industrial-scale production of inactivated vaccines, thereby promoting the healthy and sustainable development of the pig industry.
[1] ZHANG B,TANG C,LIAO M,et al.Update on the pathogenesis of Haemophilus parasuis infection and virulence factors[J].Veterinary Microbiology,2014,168(1):1-7.
[2] DUAN Y,HAO Y,FENG H P,et al.Research progress on Haemophilus parasuis vaccines[J].Frontiers in Veterinary Science,2025,12:1492144.
[3] HAESEBROUCK F,PASMANS F,CHIERS K,et al.Efficacy of vaccines against bacterial diseases in swine:what can we expect?[J].Veterinary Microbiology,2004,100(3/4):255-268.
[4] 徐冰冰，雷庆子，曾伟主，等.高密度发酵产酪氨酸酚裂解酶及催化合成L-DOPA[J].食品与发酵工业，2019,45(12):7-14.XU B B,LEI Q Z,ZENG W Z,et al.High-density fermentation for preparing tyrosine phenol lyase and application in L-DOPA synthesis[J].Food and Fermentation Industries,2019,45(12):7-14.
[5] 刘鹏，李鹏昊，张翼，等.猪肺炎支原体HN0613株高密度发酵工艺研究及效力评价[J].畜牧与饲料科学，2018,39(11):10-15,23.LIU P,LI P H,ZHANG Y,et al.High-density fermentation process of Mycoplasma hyopneumoniae HN0613 strain and its immune efficacy evaluation[J].Animal Husbandry and Feed Science,2018,39(11):10-15,23.
[6] SHI X Y,LIU Y,DAI J Y,et al.A novel integrated process of high cell-density culture combined with simultaneous saccharification and fermentation for ethanol production[J].Biomass & Bioenergy,2019,121:115-121.
[7] ZHANG G C,TURNER T L,JIN Y S.Enhanced xylose fermentation by engineered yeast expressing NADH oxidase through high cell density inoculums[J].Journal of Industrial Microbiology & Biotechnology,2017,44(3):387-395.
[8] LIU W,PANG J,WU D,et al.Hydrogen production by a novel Klebsiella pneumoniae strain from sheep rumen uses corn straw as substrate[J].Energy,2023,282:128210.
[9] 左梦楠，刘伟，全琦，等.乳酸菌高密度培养技术的研究进展[J].食品工业科技，2022,43(19):436-445.ZUO M N,LIU W,QUAN Q,et al.Research progress of lactic acid bacteria high-density culture technology[J].Science and Technology of Food Industry,2022,43(19):436-445.
[10] 程立坤，付强，张莎莎，等.副产物乳酸对猪链球菌疫苗株ST171发酵的影响[J].中国预防兽医学报，2012,34(3):227-231.CHENG L K,FU Q,ZHANG S S,et al.Effect of the lactic acid by-prodcut on fermentation cultivation of swine Streptococcosis vaccine strain(ST171)[J].Chinese Journal of Preventive Veterinary Medicine,2012,34(3):227-231.
[11] 曹毅.猪链球菌2型疫苗菌株的大规模发酵工艺优化研究[D].武汉：华中农业大学，2018.CAO Y.Optimization on the conditions of large-scale fermentation of Streptococcus suis type 2 vaccine strain[D].Wuhan:Huazhong Agricultural University,2018.
[12] 苗立中，王艳，付强，等.副猪嗜血杆菌高密度发酵条件的优化及初步应用[J].中国畜牧兽医，2014,41(9):230-234.MIAO L Z,WANG Y,FU Q,et al.Optimization and preliminary application of high density fermentation conditions of Haemophilus parasuis[J].China Animal Husbandry & Veterinary Medicine,2014,41(9):230-234.
[13] 林敏，邓舜洲，朱芝秀，等.猪细菌性呼吸道疾病病原的分离鉴定及抑菌试验[J].黑龙江畜牧兽医，2020(10):70-74,151.
[14] KUYPERS M M M,MARCHANT H K,KARTAL B.The microbial nitrogen-cycling network[J].Nature Reviews Microbiology,2018,16(5):263-276.
[15] GU W,CHEN S W,CHEN G P,et al.Enhancement of Haemophilus parasuis serovar 5 yields by medium optimization[J].Letters in Applied Microbiology,2015,61(1):44-49.
[16] 苗森，牛得权，张阳阳，等.基于响应面分析的高抗原活性猪链球菌2型疫苗培养基的研制与效果评价研究[J].饲料研究，2024,47(1):86-92.MIAO S,NIU D Q,ZHANG Y Y,et al.Development and effect evaluation of Streptococcus suis type 2 vaccine medium with high antigenic activity based on response surface analysis[J].Feed Research,2024,47(1):86-92.
[17] 关丽君.猪多杀性巴氏杆菌A型和D型二价灭活疫苗的研究[D].长春：吉林大学，2023.GUAN L J.Study on the bivalent inactivated vaccine of Pasteurella multocida serogroups A and D in swine[D].Changchun:Jilin University,2023.
[18] PAUSTIAN M L,MAY B J,KAPUR V.Transcriptional response of Pasteurella multocida to nutrient limitation[J].Journal of Bacteriology,2002,184(13):3734-3739.
[19] 马林丽，徐国强，张秋萍，等.优化培养基组分提高猪链球菌2型NT15B菌株活菌数的研究[J].中国畜牧兽医，2024,51(7):2776-2786.MA L L,XU G Q,ZHANG Q P,et al.Study on the optimization of medium composition to increase the viable counts of Streptococcus suis type 2 NT15B strain[J].China Animal Husbandry & Veterinary Medicine,2024,51(7):2776-2786.
[20] 冯志伟.Pediococcus acidilactici IMAU95219增殖培养基及高密度培养工艺优化[D].呼和浩特：内蒙古农业大学，2020.FENG Z W.Optimization of enrichment medium and high cell density cultivation of Pediococcus acidilactici IMAU95219[D].Hohhot:Inner Mongolia Agricultural University,2020.
[21] RAHAMN M T,KARIM M M.Metallothionein:a potential link in the regulation of zinc in nutritional immunity[J].Biological Trace Element Research,2018,182(1):1-13.
[22] 庞建，刘占英，郝敏，等.添加稀土离子提高嗜热梭菌发酵微晶纤维素生产乙醇的产率[J].稀土，2016,37(3):134-139.PANG J,LIU Z Y,HAO M,et al.Rare earth ions improve yield of ethanol produced with C.thermocellum on avicel[J].Chinese Rare Earths,2016,37(3):134-139.
[23] GATTUSO A,GIANFRANCESCHI M V,SONNESSA M,et al.Optimization of a real time PCR based method for the detection of Listeria monocytogenes in pork meat[J].International Journal of Food Microbiology,2014,184:106-108.
[24] CHELLADURAI K S,CHRISTYRAJ J D S,RAJAGOPALAN K,et al.Alternative to FBS in animal cell culture—an overview and future perspective[J].Heliyon,2021,7(8):e07686.
[25] GSTRAUNTHALER G,LINDL T,van de VALK J,et al.A plea to reduce or replace fetal bovine serum in cell culture media[J].Cytotechnology,2013,65(5):791-793.
[26] ROSSAN MATHEWS M G,SUBRAMANIAM R,VENKATACHALAM S,et al.Biochemical and functional characterization of heat-inactivated coelomic fluid from earthworms as a potential alternative for fetal bovine serum in animal cell culture[J].Scientific Reports,2024,14(1):5606.
[27] 王凤杰，刘万，段文龙，等.多杀性巴氏杆菌的分离鉴定和全基因组测序分析[J].中国预防兽医学报，2024,46(7):666-673.WANG F J,LIU W,DUAN W L,et al.Isolation,identification and whole genome sequencing analysis of Pasteurella multocida[J].Chinese Journal of Preventive Veterinary Medicine,2024,46(7):666-673.
[28] BAK H,RIISING H J.Protection of vaccinated pigs against experimental infections with homologous and heterologous Hoemophilus parasuis[J].Veterinary Record,2002,151(17):502-505.
[29] SCHUWERK L,HOELTIG D,WALDMANN K H,et al.Sero-and apx-typing of German Actinobacillus pleuropneumoniae field isolates from 2010 to 2019 reveals a predominance of serovar 2 with regular apx-profile[J].Veterinary Research,2021,52(1):10.
[30] 闵兆升，郭会明，颜旭，等.巴斯德毕赤酵母(P.pastoris)高密度发酵研究进展[J].生物技术通报，2014(3):42-49.MIN Z S,GUO H M,YAN X,et al.Progress of Pichia pastoris engineering bacteria on high-density fermentation[J].Biotechnology Bulletin,2014(3):42-49.
[31] GASPARI E,MALACHOWSKI A,GARCIA-MORALES L,et al.Model-driven design allows growth of Mycoplasma pneumoniae on serum-free media[J].NPJ Systems Biology and Applications,2020,6(1):33.
[32] KREITMAYER D,GOPIREEDDY S R,AKI Y,et al.Scale-up analysis of geometrically dissimilar single-use bioreactors[J].Biotechnology Bioengineering,2023,120(11):3381-3395.
[33] 宋艳梅.膜片式微孔曝气器强化能质传递促进微藻固定CO2研究[D].杭州：浙江大学，2022.SONG Y M.Strengthening energy and mass transfer with diaphragm microporous aerators to promote CO2 fixation by microalgae[D].Hangzhou:Zhejiang University,2022.
[34] 陈珊珊.搅拌釜式生物反应器流动传热特性分析及设计优化[D].合肥：安徽建筑大学，2023.CHEN S S.Flow and heat transfer characteristics analysis and design optimization of stirred tank bioreactor[D].Hefei:Anhui Jianzhu University,2023.
[35] CHENG L K,LI F,LI S G,et al.A novel nicotinamide adenine dinucleotide control strategy for increasing the cell density of Haemophilus parasuis[J].Biotechnology Progress,2019,35(3):e2794.
[36] ZHANG L W,XU H,CHENG H J,et al.Transcriptional regulation of cellobiose utilization by PRD-domain containing Sigma54-dependent transcriptional activator(CelR) and catabolite control protein(CcpA) in Bacillus thuringiensis[J].Frontiers in Microbiology,2024,15:1160472.
[37] WILLENBORG J,de GREEFF A,JAREK M,et al.The CcpA regulon of Streptococcus suis reveals novel insights into the regulation of the streptococcal central carbon metabolism by binding of CcpA to two distinct binding motifs[J].Molecular Microbiology,2014,92(1):61-83.
[38] CUI J N,HU W,LIU Y X,et al.Isolation and screening of high-yielding α-amylase mutants of Bacillus subtilis by heavy ion mutagenesis[J].Applied Biochemistry and Biotechnology,2023,195(1):68-85.
[39] 王媛，王永红.人工神经网络和响应面法优化黑曲霉发酵产淀粉酶[J].华东理工大学学报(自然科学版),2024,50(6):840-849.WANG Y,WANG Y H.Optimization of amylase production in Aspergillus niger fermentation by artificial neural network and response surface method[J].Journal of East China University of Science and Technology(Natural Science Edition),2024,50(6):840-849.
[40] JIANG R J,XIANG M Y,CHEN W T,et al.Biofilm characteristics and transcriptomic analysis of Haemophilus parasuis[J].Veterinary Microbiology,2021,258:109073.
[41] 张丙周.副猪嗜血杆菌LuxS/AI-2群体感应系统研究[D].武汉：华中农业大学，2020.ZHANG B Z.The research of LuxS/AI-2 quorum sensing system in Haemophilus parasuis[D].Wuhan:Huazhong Agricultural University,2020.
[42] ZHANG B Z,KU X G,ZHANG X Q,et al.The AI-2/luxS quorum sensing system affects the growth characteristics,biofilm formation,and virulence of Haemophilus parasuis[J].Frontiers in Cellular Infection Microbiology,2019,9:62.
[43] WEN Y P,WEN Y P,WEN X T,et al.OxyR of Haemophilus parasuis is a global transcriptional regulator important in oxidative stress resistance and growth[J].Gene,2018,643:107-116.
Basic Information:
China Classification Code:TQ920.6;S852.61
Citation Information:
[1]MA Yongkang,HAN Si'e,SU Xiaoming ,et al.Research Progress in High-Density Fermentation Technology of Porcine Bacterial Pathogens[J].Chemistry ＆ Bioengineering,2026,43(09):9-15.
Fund Information:
国家重点研发计划项目(2024YFD1800402); 呼和浩特市科技创新领域人才项目(2023RC-联合体-2)
2026-09-15
2026-09-15